Neurohumoral regulation of airway contractile responses.

strictor agonists. Together, these data suggest a role for the NANC inhibitory nervous system in preventing or attenuating bronchospasm. The functional significance ofthe airway NANC inhibitory system remains to be defined. It has been suggested that a defect in the function ofairway NANC inhibitory innervation may contribute to the elevated airway reactivity observed in asthmatic individuals. The observation that ganglionic blockade does not enhance the airway reactivity ofnormal subjects would argue against such a contention,’#{176} since efferent autonomic nerve impulse traffic from the central nervous system to the airways would be blocked. However, bronchomotor responsiveness in normal subjects may be affected by nervous (eg, adrenergic and NANC) and non-nervous (eg, arachidonic acid metabolite) inhibitory influences. Nonnervous influences may be sufficient to regulate airway reactivity under conditions ofautonomic blockade. As such, inhibition of both neural and non-neural influences may be necessary to induce a state of bronchial hyperreactivity in normal subjects. In addition, a local reflex may exist in the lung to regulate airway responsiveness, such that an axoaxonal connection would exist between afferent nerves and postganglionic NANC inhibitory nerves. This local reflex would allow the conduction ofaction potentials from afferent nerves to efferent NANC nerves without the involvement of the central nervous system and peripheral autonomic ganglia. Precise determination of the role of the NANC inhibitory system in the regulation of bronchomotor tone under physiologic and pathophysiologic conditions requires the use ofa specific NANC inhibitory receptor antagonist, which has yet to be developed. Aside from effects on airway smooth muscle, the NANC inhibitory system may regulate other lung functions, such as mucus secretion, mediator release or pulmonary vascular tone, and epithelial or endothelial permeability. Exploration of these other possible regulatory roles ofthe NANC system may provide valuable insights into the normal and abnormal physiology of the lung.